Myocardial ischemia is commonly encountered in patients with coronary artery disease and particularly during cardiac surgical procedures. The overall objective of this proposal is to define certain metabolic and functional consequences of myocardial ischemia, which if understood will enhance patient management and improve clinical results. Myocardial metabolic gradients during ischemia in normal and hypertrophied hearts will be investigated and specific pharmacologic therapies designed to slow metabolism during ischemia will be tested. Chronic conscious dog heart models of ischemic heart disease will be employed using techniques of digital sonomicrometry, solid state micromanometry, doppler coronary blood flow, conductance ventricular volumetry and catheter oxymetry to assess regional and global consequences of acute ischemia. Measurements of regional myocardial high energy phosphate compounds and myocardial energetics will be related to regional myocardial function to enhance understanding of the basic processes of ischemia and reperfusion. Serial measurements of ventricular function will be obtained in patients after cardiac operations, and the rate and degree of normalization of function during reperfusion after hypothermic cardioplegic arrest will be related to the adequacy of myocardial protection and revascularization. Ion flux measured by tissue microelectrodes and by radionuclide techniques will be evaluated as an approach to identify myocardial injury. Techniques which appear promising for definition of injury will be applied to patients at the time of cardiac surgical procedures. Completion of this investigation is apt to substantially increase our understanding of the metabolic and functional consequences of myocardial ischemia. Both the understanding and methodology resulting from this investigation can be applied to management of patients with similar forms of ischemic heart disease.